This research is directed toward gaining an understanding of the mechanism of the biological effect of carcinogens and/or mutagens by studying the chemical reactions of various alkylating agents, of differing effects, acting on 1) nucleosides and nucleotides, 2) synthetic polynucleotides, and 3) RNA and DNA in vitro and in vivo. The work falls in several areas, namely 1) chemical studies of the alkylation, by ethylating and methylating agents, of the nucleosides, uridine, thymidine and cytidine and the nucleotides uridylic acid and thymidylic acid; 2) alkylation of poly U; 3) ethylation of RNA and DNA with ethylnitrosourea and ethylnitrosoguanidine; and 4) preparation or O2-alkyluridine, O4-alkylcytidine and their subsequent phosphorylation to the diphosphates in order to attempt to polymerize them into high molecular weight polynucleotides. BIBLIOGRAPHIC REFERENCES: "The Specificity of Different Classes of Ethylating Agents Toward Various Sites in RNA" B. Singer and H. Fraenkel-Conrat, Biochemistry, 14, 772-782 (1975). "Reactions of Oncogenic Alkylating Agents with Nucleic Acids" B. Singer and H. Fraenkel-Conrat, Proceedings of the American Association for Cancer Research, 321 (1975).